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Tumor Microenvironment Responsive Shape-Reversal Self-Targeting Virus-Inspired Nanodrug for Imaging-Guided Near-Infrared-II Photothermal Chemotherapy.
ACS Nano ( IF 15.8 ) Pub Date : 2019-10-29 , DOI: 10.1021/acsnano.9b05425 Yang Li 1, 2, 3 , Jinyan Lin 2 , Peiyuan Wang 1, 2, 3 , Qiang Luo 1, 2, 3 , Huirong Lin 4 , Yun Zhang 1, 3 , Zhenqing Hou 5 , Jingfeng Liu 1, 2, 3 , Xiaolong Liu 1, 2, 3
ACS Nano ( IF 15.8 ) Pub Date : 2019-10-29 , DOI: 10.1021/acsnano.9b05425 Yang Li 1, 2, 3 , Jinyan Lin 2 , Peiyuan Wang 1, 2, 3 , Qiang Luo 1, 2, 3 , Huirong Lin 4 , Yun Zhang 1, 3 , Zhenqing Hou 5 , Jingfeng Liu 1, 2, 3 , Xiaolong Liu 1, 2, 3
Affiliation
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Tumor microenvironment responsive multimodal synergistic theranostic strategies can significantly improve the therapeutic efficacy while avoiding severe side effects. Inspired by the fact that special morphology could enhance photothermal conversion efficiency (PCE) and cellular delivery, we developed an acidic tumor microenvironment responsive shape-reversal metal–organic virus-inspired nanodrug for enhancing near-infrared (NIR)-II PCE, increasing cell adhesion, and activating tumor targeting. First, a NIR-I fluorescence probe (IR825), a chemo-drug (pemetrexed, PEM), and a rare-earth metal ion (Nd(III)) were chosen to synthesize a virus-like nanodrug via coordination-driven assembly. Then, the spike-like surface of the nanodrug was further camouflaged by an acidity-sensitive poly(ethylene glycol) “shell” to create virus-core and sphere-shell hierarchical nanoassemblies, which could efficiently prevent immune clearance and prolong systemic circulation. Interestingly, the acidic tumor microenvironment could trigger the shell detachment of nanoassemblies for shape reversal to produce a virus-like surface followed by re-exposure of PEM to synergistically amplify the cellular internalization while enhancing NIR-II PCE. By utilizing the shell-detached virus-like nanodrug core, the tumor microenvironment specific enhanced NIR-II photothermal chemotherapy can be realized under the precise guidance of fluorescence/photoacoustic imaging, thereby achieving complete tumor elimination without recurrence in a single treatment cycle. We envision that integrating the tumor microenvironment responsive ability with “sphere-to-virus” shape reversal will provide a promising strategy for biomimetic targeted cancer therapy.
中文翻译：
肿瘤微环境响应形状逆转自靶向病毒启发的纳米药物成像引导的近红外II光热化学疗法。
肿瘤微环境响应性多峰协同治疗方法可以显着提高治疗效果，同时避免严重的副作用。受特殊形态可以增强光热转换效率（PCE）和细胞传递的事实启发，我们开发了酸性肿瘤微环境响应形状逆转金属-有机病毒启发的纳米药物，用于增强近红外（NIR）-II PCE，增加细胞粘附，并激活肿瘤靶向。首先，选择NIR-1荧光探针（IR825），化学药物（pemetrexed，PEM）和稀土金属离子（Nd（III））来通过协调驱动的装配。然后，纳米药物的尖峰状表面被酸敏感性聚（乙二醇）“壳”进一步掩盖，以形成病毒核和球壳分层的纳米组件，从而可以有效地防止免疫清除并延长全身循环。有趣的是，酸性肿瘤微环境可能会触发纳米组件的外壳分离，从而发生形状反转，从而产生病毒样表面，然后再次暴露PEM以协同放大细胞内在化，同时增强NIR-II PCE。通过利用脱壳的病毒样纳米药物核心，可以在荧光/光声成像的精确指导下实现肿瘤微环境特异性增强的NIR-II光热化学疗法，从而实现了完整的肿瘤消除，并且在单个治疗周期中没有复发。我们设想将肿瘤微环境反应能力与“球形病毒”形状逆转相结合将为仿生靶向癌症治疗提供有前途的策略。
更新日期：2019-10-29
中文翻译：
肿瘤微环境响应形状逆转自靶向病毒启发的纳米药物成像引导的近红外II光热化学疗法。
肿瘤微环境响应性多峰协同治疗方法可以显着提高治疗效果，同时避免严重的副作用。受特殊形态可以增强光热转换效率（PCE）和细胞传递的事实启发，我们开发了酸性肿瘤微环境响应形状逆转金属-有机病毒启发的纳米药物，用于增强近红外（NIR）-II PCE，增加细胞粘附，并激活肿瘤靶向。首先，选择NIR-1荧光探针（IR825），化学药物（pemetrexed，PEM）和稀土金属离子（Nd（III））来通过协调驱动的装配。然后，纳米药物的尖峰状表面被酸敏感性聚（乙二醇）“壳”进一步掩盖，以形成病毒核和球壳分层的纳米组件，从而可以有效地防止免疫清除并延长全身循环。有趣的是，酸性肿瘤微环境可能会触发纳米组件的外壳分离，从而发生形状反转，从而产生病毒样表面，然后再次暴露PEM以协同放大细胞内在化，同时增强NIR-II PCE。通过利用脱壳的病毒样纳米药物核心，可以在荧光/光声成像的精确指导下实现肿瘤微环境特异性增强的NIR-II光热化学疗法，从而实现了完整的肿瘤消除，并且在单个治疗周期中没有复发。我们设想将肿瘤微环境反应能力与“球形病毒”形状逆转相结合将为仿生靶向癌症治疗提供有前途的策略。
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